The goal of the proposed project is to gain quantitative information regarding the therapeutic potential of combining common anti-tumor agents including radiation, hyperthermia, and chemotherapy. Multicell spheroids, an in vitro tumor model, will be exposed to the single or combined modalities, and the viability of each of the cycling, noncycling and hypoxic cell populations of the spheroid after treatment will indicate both the effiacy and specificity of each treatment regimen. In addition to cell viability studies using colony formation as the experimental endpoint, other indicators of spheroid response will be followed, including regression rate, regrowth rate, cellularity, and the repair and repopulation of te spheroid cells in situ. The timing and sequencing of various agents for an optimum response after a single treatment will be determined, and these results will be extended to multifraction therapy regimens where we anticipate that the therapeutic effectiveness can be maximized. We hope that these results will aid in both the planning and rationalization of cancer treatment in man.